Method and system for the production of cells and cell products and applications thereof

Abstract

A cell culture system for the production of cells and cell derived products includes a reusable instrumentation base device incorporating hardware to support cell culture growth. A disposable cultureware module including a cell growth chamber is removably attachable to the instrumentation base device. The base device includes microprocessor control and a pump for circulating cell culture medium through the cell growth chamber. The cultureware module is removably attached to the instrumentation base device. Cells are introduced into the cell growth chamber and a source of medium is fluidly attached to the cultureware module. Operating parameters are programmed into the microprocessor control. The pump is operated to circulate the medium through the cell growth chamber to grow cells or cell products therein. The grown cells or cell products are harvested from the cell growth chamber and the cultureware module is then disposed.

What is claimed is: 
     
       1. A cell culture system for the production of cells and cell derived products comprising:
 a reusable instrumentation base device incorporating hardware to support cell culture growth; and 
 at least one disposable cell cultureware module removably attachable to said instrumentation base device, said module including a cell growth chamber and 
 at least one rotary actuator valve for controlling circulation of cell culture medium through at least one elastomer medium flow circuit in said cultureware module, said at least one rotary actuator valve including a housing having an inner passage and at least one port for receiving the at least one elastomer medium flow circuit, and a valve body having first and second ends located within said inner passage of said valve housing and rotatable about a longitudinal axis within said valve housing, said valve body including a plurality of cam surfaces and angular sections along a length thereof to sequentially compress and open the at least one elastomer medium flow circuit as said valve body rotates within said valve housing, wherein said plurality of cam surfaces compresses the at least one elastomer medium flow circuit by making direct contact with a segment of the at least one elastomer medium flow circuit. 
 
     
     
       2. The cell culture system of  claim 1 , wherein said instrumentation device includes a pump for circulating cell culture medium through the at least one elastomer medium flow circuit in said cultureware module. 
     
     
       3. The cell culture system of  claim 2 , wherein said pump moves growth factor or other supplements through the at least one elastomer medium flow circuit into said cell growth chamber and removes product harvest from said cell growth chamber. 
     
     
       4. The cell culture system of  claim 1 , wherein said instrumentation device includes a cool storage area for storing growth factor or other supplements and product harvest, and wherein said instrumentation device includes a heating mechanism for heating the cell growth chamber to promote growth and production. 
     
     
       5. The cell culture system of  claim 4 , wherein said at least one cultureware module includes an inlet and outlet port, said inlet and outlet ports being constructed and arranged to align with air ports of said instrument device such that the heating mechanism forces heated air into said at least one cultureware module from said instrument device. 
     
     
       6. The cell culture system of  claim 1 , wherein said instrumentation base device includes a multi-channel peristaltic pump for moving fresh basal media into said at least one cultureware module, wherein said multi-channel peristaltic pump has discrete, variable output control for each channel, and wherein said at least one cultureware module further comprises a pump cassette, wherein said pump cassette is structured to hold multiple peristaltic tubing segments, and wherein said pump cassette is insertable into an interface on said instrumentation base device and allows for said tubing segments to be loaded into said multi-channel peristaltic pump in said instrumentation base device at the same time. 
     
     
       7. The cell culture system of  claim 2 , wherein said at least one cultureware module includes a gas blending mechanism in communication with the cell growth chamber, wherein the cell culture system further comprises a pH sensor disposed in said at least one cultureware module to control the pH of the cell culture medium, wherein the gas blending mechanism includes a gas exchange cartridge that provides oxygen and adds or removes carbon dioxide to the medium to support cell metabolism, wherein the gas exchange cartridge has an inlet end and a discharge end, and wherein the cell culture system further comprises a carbon dioxide sensor in fluid communication with the discharge end of the gas exchange cartridge for measuring the carbon dioxide level of the cell culture medium. 
     
     
       8. The cell culture system of  claim 1 , wherein said at least one cultureware module includes a plurality of interface features integrated into the module that mate with instrument interface features in said instrumentation device. 
     
     
       9. The cell culture system of  claim 2 , wherein said at least one cultureware module includes sensors for sensing fluid circulation rate, temperature and pH of the cell culture medium. 
     
     
       10. The cell culture system of  claim 1 , wherein the cell growth chamber comprises a bioreactor that provides cell space and medium component exchange, and wherein the bioreactor has a flexible outer body. 
     
     
       11. The cell culture system of  claim 1 , wherein said at least one cultureware module includes a fluid cycling unit disposed therein to cycle and maintain fluid volumes within the cell growth chamber, and wherein the fluid cycling unit includes a non-rigid reservoir and a second flexible reservoir in fluid communication with the first reservoir to cause elevated pressure in the first reservoir. 
     
     
       12. The cell culture system of  claim 1 , further comprising a plurality of disposable containers for harvest collection and flushing removably connected to said at least one cultureware module. 
     
     
       13. The cell culture system of  claim 1 , further comprising a drive device located within said instrumentation base device or controlling the rotation of said valve body within said valve housing. 
     
     
       14. The cell culture system of  claim 13 , wherein said drive device includes feedback position control and is controlled by a microprocessor to automate the rotation of said valve body. 
     
     
       15. The cell culture system of  claim 1 , wherein said valve housing is located in said cultureware module. 
     
     
       16. The cell culture system of  claim 15 , wherein said valve housing is formed integrally with said cultureware module. 
     
     
       17. The cell culture system of  claim 3 , wherein said at least one rotary selection valve is in fluid communication with said pump to control the medium flow through said cultureware module. 
     
     
       18. The cell culture system of  claim 1 , wherein said at least one elastomer medium flow circuit comprises a length of elastomer tubing connected to a source of the cell culture medium. 
     
     
       19. The cell culture system of  claim 18 , wherein said valve housing includes an inner wall and said at least one port extends through said wall into said inner passage of said housing. 
     
     
       20. The cell culture system of  claim 19 , wherein said elastomer tubing extends through said at least one port into said inner passage where said tubing is positioned between said inner wall of said housing and said valve body. 
     
     
       21. The cell culture system of  claim 1 , wherein said cam surfaces comprise cylindrical portions disposed along a length of said valve body. 
     
     
       22. The cell culture system of  claim 21 , wherein said valve body includes a flat upper portion formed along a length of said valve body and said angular sections are offset from said upper portion. 
     
     
       23. The cell culture system of  claim 1 , wherein said at least one rotary actuator valve includes a plurality of said ports for receiving a plurality of the at least one elastomer medium flow circuits, and wherein said plurality of cam surfaces compresses the plurality of elastomer medium flow circuits b r making direct contact with a segment of each elastomer medium flow circuit. 
     
     
       24. The cell culture system of  claim 23 , wherein the plurality of elastomer medium flow circuits comprise lengths of elastomer tubing connected to a source of the cell culture medium, wherein said valve housing includes an inner wall and said at least one port extends through said wall into said inner passage of said housing, and wherein said elastomer tubing extends through said at least one port into said inner passage where said tubing is positioned between said inner wall of said housing and said valve body. 
     
     
       25. A method for the expansion or growth of cells, comprising providing the cell culture system of  claim 1 , introducing cells into the cell growth chamber of the cell culture system, growing cells or cell products from the introduced cells, and harvesting the grown cells or cell products from the cell growth chamber.